This application is for continued support of the administrative and research cores of the BF Stolinsky Laboratories Mental Retardation Research Center at the University of Colorado Health Sciences Center. This MRRC began its operations in 1968, and most of its investigators and core are now housed in a new and larger facility on the UCHSC campus. The research of all investigators that utilize the cores impacts substantially on mental retardation and developmental disabilities. Most of their work is on heritable cause of central nervous system dysfunction, with a primary focus on inborn errors of metabolism and specifically on disorders of mitochondria. Substantial effort is also directed to environmental causes of MRDD, including trace metal deficiencies and viral infections, and how these conditions affect neuropsychological processes and cognitive development. Studies on genetic (metabolic) causes of central nervous system dysfunction focus on glutaric acidemia type I and II (Goodman & Frerman), cystathionine beta-synthase deficiency (Kraus), propionic acidemia (Kraus), and Down syndrome (Patterson & Gardiner)); the primary aim of these studies is to better understand pathogenesis, so that efforts to treat can have a more science-based rationale. Studies of environmental causes of MRRD examine the impact of zinc deficiency in infancy and gestation (Krebs), and of latent viral infections in the newborn period (Crnic) on subsequent cognition. Others focus on developmental (learning) disorders such as schizophrenia (Ross, Leonard), dyslexia, attention deficit hyperactivity disorder, and autism (Rogers & Pennington; early events in neuronal development of the human CNS (Pfenninger); and neuromuscular defects related to sodium channels (Caldwell). Core facilities for which support is sought include: a) administration, b) Cell Biology, c) Chemistry/Mass Spectrometry, e) Large Insert Library Screening, f) Developmental Neuropsychology, g) Animal Housing and Assessment, and h) Instrument maintenance and Glassware Washing services. Core e) is new to this application. We also propose an association with the MRRC at Baylor College of Medicine, in which investigators at each institute can learn techniques from one another and, in some cases, utilize each others cores.